Activity of MMP-2, MMP-8 and MMP-9 in serum as a marker of progression of alcoholic liver disease in people from Lublin Region, eastern Poland
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Department of Internal Medicine, Medical University of Lublin, Poland
Department of Medical Chemistry, Medical Univeristy of Lublin, Poland
Department of Clinical Immunology, Medical University of Lublin, Poland
Department of Mathematics and Medical Biostatistics, Medical University of Lublin, Poland
Department of Nephrology, Medical University of Lublin, Poland
Ann Agric Environ Med. 2015;22(2):325-328
In alcoholic liver cirrhosis, normal liver cells are replaced by scar tissue (fibrosis). Liver fibrosis is a dynamic process in which activated hepatic stellate cells are involved in the synthesis of matrix proteins and the regulation of matrix degeneration. The aim of the presented study was to assess the usefulness of MMP-2, MMP-8 and MMP-9 as diagnostic markers of alcoholic liver disease. Sixty patients with alcoholic liver cirrhosis were randomly enrolled during hospitalization in departments of hospitals from the Lublin Region in eastern Poland. The stage of cirrhosis was estimated according to Child-Turcotte-Pugh criteria (Child-Pugh score) as P- Ch A, P-Ch B, P-Ch C. The control group consisted of 10 healthy persons without liver disease, who did not drink alcohol. Additionally, a group of alcoholics without liver cirrhosis was included in the study. Blood sample were obtained, and after centrifuge, serum was collected for further analysis. The activity of MMP-2, MMP-8 and MMP-9 in the blood plasma of the patients and the control group were measured by using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Activity of MMP-2, MMP-8 and MMP-9 in patients with liver cirrhosis were increased gradually according to Child-Pugh stages. The activity of MMP-2, MMP-8, MMP-9 were the highest in patients with liver cirrhosis stage C. MMP-2, MMP-8, MMP-9 concentrations in the people with liver cirrhosis (stage C) were significantly increased compared to controls. A significant difference were observed between activity MMP-2 in control group, alcoholics without liver cirrhosis, and those with liver cirrhosis (stages A, B, C according Child-Pugh score). MMP-2, MMP-8 and MMP-9 may be markers of alcoholic liver cirrhosis in the alcoholics. Elevated levels of MMP-2, MMP-8 and MMP-9 in the alcoholic patients indicated that cirrhosis has developed. The most sensitive is MMP-2, because the activity of this parameter is increased in all liver cirrhosis stages. MMP-8 and MMP-9 activity were significantly elevated only in serum patients with advanced liver cirrhosis, compared to controls.
Savolainen VT, Liesto K, Mannikko A, Penttila A, Karhunen PJ. Alcohol consumption and alcoholic liver disease: evidence of a threshold level of effects of ethanol. Alcohol Clin Exp Res. 1993; 17: 1112–1117.
Loft S, Olesen KL, Dossing M. Increased susceptibility to liver disease in relation to alcohol consumption in women. Scand J Gastroenterol. 1987; 22: 1251–1256.
Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005; 115: 209–218.
Popper H. Pathologic aspects of cirrhosis. Am J Pathol. 1977; 49: 707–721.
Moreno M, Bataller R. Cytokines and renin-angiotensin system signaling in hepatic fibrosis. Clin Liver Dis. 2008; 12: 825–852.
Iredale J. Tissue inhibitors of metalloproteinases in the liver fibrosis. Int J Biochem Cell Biol. 1997; 29: 43–54.
Winwood PJ, Schuppan D, Iredale JP, Kawser ChA, Docherty AJP, Arthur MJP. Kupffer cell-derived 95-kd type IV collagenase/-gelatinase B characterization and expression in cultured cells. Hepatology 1995; 22: 304–315.
Murphy G, Docherty AJP. The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol. 1992; 7: 120–125.
Marsano LS, Mendez Ch, Hill D, Barve S, McClain CJ. Diagnosis and treatment of alcoholic liver disease and its complications. Alcohol Res Health. 2003; 27: 247–256.
Corcoran ML, Hewitt RE, Kleiner Jr DE, Stetler-Stevenson WG. MMP-2: expression, activation and inhibition. Enzyme Protein 1996; 49: 7–19.
Lichtinghagen R, Michels D, Haberkorn CI, Arndt B, Bahr M, Flemming P Manns MP, Boeker KH. MMP-2, MMP-7, and TIMP-1 are closely related to the fibroproliferative process in the liver during chronic hepatitis C. J Hepatol. 2001; 34: 239–247.
Takahara T, Furui K, Yata Y, Jin B, Zhang LP, Nambu S, Sato H, Seiki M, Watanabe A. Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology 1997; 26: 1521–1529.
Murawaki Y, Yamada S, Ikuta Y, Kawasaki H. Clinical usefulness of serum matrix metallo-proteinase-2 concentration in patients with chronic liver disease. J Hepatol. 1999; 30: 1090–1098.
Owen CA, Campbell EJ. The cell biology of leukocyte-mediated proteolysis. J Leukoc Biol. 1999; 65: 137–150.
Swystun V, Chen L, Factor P, Siroky B, Bell PD, Matalon S. Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+. Am J Physiol Lung Cell Mol Physiol. 2005; 288: 820–830.
Arthur MJ, Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2000; 279: 245–249.
Berton G. Degranulation. In: Gallin JI, Snyderman R. Inflammation: Basic principles and clinical correlates. 3 rd ed. Philadelphia, 1999.p.703–719.
Harty MW, Huddleston HM, Papa EF, Puthawala T, Tracy AP, Ramm GA, Gehring S, Gregory SH, Tracy TF. Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity. Surgery 2005; 138: 313–320.
Wielockx B, Lannoy K, Shapiro SD Itoh T, Itohara S, Vandekerckhove J, Libert C. Inhibition of matrix metalloproteinases bloks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapy. Nat Med. 2001; 7: 1202–1208.
D’Amico, F. Consolo M, Amoroso A, Skarmoutsou E, Mauceri B, Stivala F, Malaponte G, Bertino G, Neri S, Mazzarino MC. Liver immunolocalization and plasma level of MMP-9 in non-alcoholic steatohepatitis (NASH) and hepatitis C infection. Acta Histochem. 2010; 112: 474–481.
Ljumovic D, Diamantis I, Alegakis AK, Kouroumalis EA. Differential expression of matrix metalloproteinases in viral and non-viral chronic liver disease. Clin Chim Acta. 2004; 349: 203–211.
Hayasaka A, Suzuki N, Fujimoto N, Iwama S, Fukuyama E, Kanda Y, Saisho H. Elevated plasma levels of matrix metalloproteinase-9 (92-kd type IV collagenase/gelatinase B) in hepatocellular carcinoma. Hepatology 1996; 24: 1058–1062.
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